Background & project objective
Main goal of the proposed project is to proposes an updated set of human toxicity effect factors via oral exposure for selected metals for reproduction/developmental effects and general non-cancer effects for inclusion into life cycle impact toxicity characterization models.
Focus is on providing an updated and consistent input dataset for deriving human toxicological effect factors for non-cancer effects that are prepared in the form of a minor corrective update of the USEtox model for the following metals: Aluminium (Al), Cobalt (Co), Copper (Cu), Manganese (Mn), Molybdenum (Mo), Nickel (Ni) and Zinc (Zn). Targeted will be chronic ED10 derived from various effect test data are used as the starting point to derive human lifetime equivalent dose-response factors for non-cancer effects using a probabilistic framework.
Project output
Main project output focuses on the three main aspects that are listed in below table.
| Aspect | Output description |
|---|---|
| Test data collection | Review available effect test data for oral exposure across global regions and jurisdictions (including NOAEL, NOEL, NEL, LOAEL, LOEL, LEL, BMD) for relevant metal ions that can be used as input to derive points of departure (PODs) as starting point for obtaining human toxicity effect factors, differentiated according to reproductive/developmental toxicity effects vs. general non-cancer toxicity effects. |
| Data selection hierarchy | For each metal, derive and discuss a possible data hierarchy for obtaining PODs, in alignment with existing recommendations, and provide recommendations how to extrapolate PODs for oral exposure as a first proxy to PODs for inhalation exposure where such data are currently missing or considered outdated or otherwise unreliable in the present USEtox inorganic substances database. |
| Data curation protocol | Derive and apply a human effect test data curation protocol to derive representative PODs for each metal ion for oral exposure, in line with the data hierarchy protocol applied to organic substances where applicable. |
| Human toxicity effect factors development | Derive human toxicity non-cancer effect factors for the two stated health endpoints (reproductive/developmental toxicity and general non-cancer toxicity) and compare them across metals with previous effect factors available in USEtox to understand and appreciate differences in the underlying data and methods, and apply a sensitivity analysis where needed to determine the relevance of potential differences in existing and updated effect factors for the considered metal ions. |
